ArticlemAbs
Differential effects of IL-2 and IL-21 on expansion of the CD4+ CD25+ Foxp3+ T regulatory cells with redundant roles in natural killer cell mediated antibody dependent cellular cytotoxicity in chronic lymphocytic leukemia.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Engineered murine IL-21-secreting leukemia cells induce granzyme BCancer immunology, immunotherapy : CII · 2023Article
- A Synthetic Disaccharide Derivative of Diphyllin, TAARD, Activates Human Natural Killer Cells to Secrete Interferon-GammaFrontiers in immunology · 2018Article
- Coevolution of Leukemia and Host Immune Cells in Chronic Lymphocytic Leukemia.Cold Spring Harbor perspectives in medicine · 2017Review
- T-cell number and subtype influence the disease course of primary chronic lymphocytic leukaemia xenografts in alymphoid mice.Disease models & mechanisms · 2015Article
- Natural Killer Cell-Based Therapies Targeting Cancer: Possible Strategies to Gain and Sustain Anti-Tumor Activity.Frontiers in immunology · 2015Review
- The natural product phyllanthusmin C enhances IFN-γ production by human NK cells through upregulation of TLR-mediated NF-κB signaling.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Regulatory T cells in chronic lymphocytic leukemia: implication for immunotherapeutic interventions.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Review
- IL-21 promotes the expansion of CD27+ CD28+ tumor infiltrating lymphocytes with high cytotoxic potential and low collateral expansion of regulatory T cells.Journal of translational medicine · 2013Article
- A phase I dose-finding trial of recombinant interleukin-21 and rituximab in relapsed and refractory low grade B-cell lymphoproliferative disorders.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Article
- Article
- Role of common-gamma chain cytokines in NK cell development and function: perspectives for immunotherapy.Journal of biomedicine & biotechnology · 2011Review
- Inflammation and survival pathways: chronic lymphocytic leukemia as a model system.Biochemical pharmacology · 2010Review
- Review
- Article
- Overview on Immunopathology of Chronic Lymphocytic Leukemia and Tumor-Associated Antigens with Therapeutic Applications.Avicenna journal of medical biotechnologyReview
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
CD4(+) CD25(+) regulatory T cells are expanded in solid and hematological malignancies including chronic lymphocytic leukemia (CLL). Several cytokines and co-stimulatory molecules are required for generation, survival and maintenance of their suppressive effect. We and others have shown direct cytotoxic effect of the novel common gamma chain cytokine interleukin (IL)-21 on primary B cells from CLL patients. Since members of this family of cytokines are known to exhibit their effects on diverse immune cells, we have examined the effects of IL-21 on CLL patient derived regulatory T cell (Treg) induction, expansion and the inhibitory effect on natural killer cells in vitro. We demonstrate here the expression of IL-21 receptor in CD4(+)CD25(High) regulatory cells from CLL patients. In contrast to IL-2, the IL-21 cytokine failed to mediate expansion of regulatory T cells or induced expression of Foxp3 in CD4(+)CD25(Intermediate) or CD4(+)CD25(Dim/-) T cells in whole blood derived from CLL patients. Interestingly, in contrast to their differential effects on expansion of the CD4(+)CD25(+)Foxp3(+)T cells, IL-2 and IL-21 exhibited a redundant role in Treg mediated suppression of NK cell mediated antibody dependent cytotoxicity function. Given the infusion related toxicities and pro-survival effect of IL-2 in CLL, these studies provide a rationale to explore IL-21 as an alternate gamma chain cytokine in CLL therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.